If inhibition is well tolerated, JMJD2C represents a promising drug target in MPN possibly for synergistic use with JAK inhibitors, as Ernst et al. very recently demonstrated that JAK2V617F-mutated cells functionally depend on JMJD2C even during exposure to Ruxolitinib [13]. The gene discussed is KDM4C; the disease is myeloproliferative neoplasm.